Abstract 3170: Comprehensive analysis of the microRNA-128 function in head and neck squamous cell carcinoma

Abstract

Abstract MicroRNAs are 22∼nucleotide-long endogenously expressed, highly conserved noncoding RNAs with important regulatory functions in proliferation, apoptosis, and metastasis. miR-128 a brain-enriched, which is transcribes from two gene copies (miR-128-1 and miR-128-2) on chromosome 2 and chromosome 3 which produce identical mature forms. miR-128 is most commonly in gliomas that have shown to function as a tumor suppressor which inhibits cell proliferation. Proteomic alterations of prostate cancer show miR-128 to down regulate cell invasiveness. Here we evaluated the role of miRNA-128 in HNSCC, to identify its putative targets and elucidate the possible mechanisms underlining the function of miR-128 in HNSCC. We established HNSCC cell lines that stably expressed individual members of the miR-128 using a lentiviral delivery system. The levels of miR-128 and their targeted proteins were analyzed by qRT-PCR and Western blot. miR-128 affinity was elucidated by MTT, colony formation, flow cytometry, and a tumor xenograft model. Two kinds of stably transfected HNSCC cell lines, including JHU-22miR-128 transfected with miR-128 and a vector control cell line JHU-22vector, were generated as a testing system. The miR-128 level in the JHU-22miR-128 cells was eleven fold higher than in JHU-22vector cells. We found that overexpression of miR-128 enable to effectively suppress cell viability (30%), decrease of proliferation (55%), and significantly reduced solid tumor growth in tumor xenografts models compared to the control groups. Transfected miR-128 cells exhibited astrocyte morphology. The inhibition mechanism of miR-128 was determined by evaluating five putative targets (BMI-1, BAG2, BAX, H3f3b, and Paip2) of miR-128. Overall, miR-128 enables to directly inhibit all these targets, but the binding affinity of miR-128 is dominantly towards to BMI-1 and BAG-2 targets. Conclusions: miR-128 exhibits anti-proliferative effects and phenotypic alteration in HNSCC by targeting multiple predicted conserved targets activity function in apoptosis, cell cycle, transcription, and translation. Our results provide a better understanding of miR-128 function in HNSCC and the potential targets to develop novel diagnostic markers and targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3170. doi:1538-7445.AM2012-3170